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Chinese yam (Dioscorea opposita Thunb. cv. Tiegun), a type of homologous medicinal plant, mainly grows in sandy soil (SCY) and loessial soil (LCY). However, the effects of the soil on the metabolites in SCY and LCY remain unclear. Herein, this study aims to comprehensively elucidate the metabolites in SCY and LCY. A UPLC-MS/MS-based, widely targeted metabolomics approach was adapted to compare the chemical composition of SCY and LCY. A total of 988 metabolites were detected, including 443 primary metabolites, 510 secondary metabolites, and 35 other compounds. Notably, 177 differential metabolites (classified into 12 categories) were identified between SCY and LCY; among them, 85.9% (152 differential metabolites) were upregulated in LCY. LCY significantly increased the contents of primary metabolites such as 38 lipids and 6 nucleotides and derivatives, as well as some secondary metabolites such as 36 flavonoids, 28 phenolic acids, 13 alkaloids, and 6 tannins. The results indicate that loessial soil can improve the nutritional and medicinal value of D. opposita. [ABSTRACT FROM AUTHOR]

Dioscorea opposita Thunb., a traditional medicinal and food homologous plant, has been used for thousands of years in folk medicine and nutritious food, partially due to the metabolites. However, detailed information on the metabolites in Dioscorea opposita Thunb. peel is still scarce. Herein, an ultra‐high‐performance liquid chromatography‐quadrupole/orbitrap high‐resolution mass spectrometry‐based metabolomics approach was used to reveal the comprehensive metabolites in Dioscorea opposita Thunb. peel. The proposed method provided tentative identification of 307 metabolites. Among them, 286 metabolites are reported herein in Dioscorea opposita Thunb. peel for the first time, namely: 87 lipids, 49 phenolic acids, 34 flavonoids, 29 amino acids and derivatives, 28 organic acids, 14 alkaloids, 10 lignans, and coumarins, eight saccharides and vitamins, six nucleotides and derivatives, two quinones, and 19 others. The obtained results highlight the importance of Dioscorea opposita Thunb. peel as a promising source of bioactive ingredients, and form a basis for future quantitative and bioavailability studies. [ABSTRACT FROM AUTHOR]

Background: Delta‐like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1‐directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1‐positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. Methods: We first characterized a homemade anti‐human DLK1 monoclonal antibody, sequenced the single‐chain Fragment variable (scFv) and integrated it into the second‐generation CAR lentiviral vector, and then developed the DLK1‐directed CAR‐T cells. The cytotoxic activities of DLK1‐directed CAR‐T cells against different HCC cells were evaluated in vitro and in vivo. Results: The genetically modified human T cells with the DLK1‐directed CARs produced cytotoxic activity against DLK1‐positive HCC cells. Additionally, the DLK1‐directed CARs enhanced T cell proliferation and activation in a DLK1‐dependent manner. Interestingly, the DLK1‐targeted CAR‐T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh‐7. Conclusion: DLK1‐directed CAR‐T cells specifically suppresses DLK1‐positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR‐T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Callicarpa kwangtungensis Chun is a traditional Chinese medicine that has various therapeutic effects. Despite its wide use in Chinese medicine, the study is still quite limited, especially its chemical compositions. In this research, an ultra‐high‐pressure liquid chromatography coupled with Q Exactive hybrid quadrupole‐orbitrap high‐resolution accurate mass spectrometry tandem mass spectrometry method was utilized to analyze its chemical compositions for the first time. As a result, a total of 124 compounds, including 20 phenylethanoid glycosides, 31 flavonoids, 36 organic acids, 26 terpenoids and 11 phenols, were identified or tentatively characterized in 30 min. Among them, 49 compounds, including 5 phenylethanoid glycosides, 12 flavonoids, 16 organic acids, 12 terpenoids, and 4 phenols, were identified in Callicarpa kwangtungensis Chun for the first time. Besides, the fragmentation pathways were also discussed. This research established a rapid and reliable method to analyze the chemical compositions of complicated herb without the process of isolation, and provide abundant information on the chemical material basis for further bioactivity and quality control studies. [ABSTRACT FROM AUTHOR]

Brg1/SMARCA4 serves as the ATPase and the helicase catalytic subunit for the multi-component SWI/SNF chromatin remodeling complex, which plays a pivotal role in governing chromatin structure and gene transcription. However, the upstream signaling pathways regulating Brg1 protein stability and its physiological contribution to carcinogenesis remain largely elusive. Here we report that Brg1 is a bona fide ubiquitin substrate of SCFFBW7. We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation. In keeping with a tumor suppressive role of FBW7 in human gastric cancer, we find an inverse correlation between FBW7 and Brg1 expression in human gastric cancer clinical samples. Mechanistically, we find that stabilization of Brg1 in gastric cancer cells suppresses E-cadherin expression, subsequently promoting gastric cancer metastasis. Hence, this previously unknown FBW7/Brg1 signaling axis provides the molecular basis and the rationale to target Brg1 in FBW7-compromised human gastric cancers. Upstream pathways regulating Brg1 stability and their role in carcinogenesis are unknown. Here they show Brg1 to be phosphorylated by CK1δ to promote its ubiquitination by SCFFBW7 (FBW7), Brg1 stabilization to promote gastric cancer metastasis, and suggest targeting Brg1 in FBW7 compromised gastric cancer. [ABSTRACT FROM AUTHOR]